Evolution__3rd_Edition

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Summary
1 The neutral theory of molecular evolution suggests
that molecular evolution is mainly due to neutral drift.
On this view, the mutations that have been substituted
in evolution were selectively neutral with respect to the
genes they replaced. Alternatively, molecular evolution
may be mainly driven by natural selection.
2 Three main observations were originally used to
argue in favor of the neutral theory: molecular evolution
has a rapid rate, its rate has a clock-like constancy,
and it is more rapid in functionally less constrained
parts of molecules.
3 One of the three arguments a from high rates of
evolution (and high levels of polymorphism) a used
the concept of genetic load and is no longer thought
conclusive.
4 The constant rate of molecular evolution gives rise
to a “molecular clock.”
5 Neutral drift should drive evolution at a stochastically
constant rate; Kimura pointed to the contrast
between uneven rates of morphological evolution and
the constant rate of molecular evolution and argued
that natural selection would not drive molecular
evolution at a constant rate.
6 For synonymous changes, evolution is faster in
lineages with shorter generation times. For nonsynonymous
change, some evidence suggests that the
rate of evolution is relatively constant independent
of generation time, and other evidence suggests that
the rate of evolution is faster in lineages with shorter
generation times.
7 The original neutral theory had difficulty explaining
certain observations, including: (i) the similar level of
polymorphism in all species, independent of population
size; (ii) the difference between synonymous and
non-synonymous sites in whether the rate of evolution
depends on generation times; and (iii) different ratios
of non-synonymous to synonymous evolution for
polymorphism within a species and divergence between
species.
8 The nearly neutral theory of molecular evolution
suggests that molecular evolution is driven by random
CHAPTER 7 / Natural Selection and Random Drift 191
drift, but includes the effect of drift on mutations with
small disadvantageous (and advantageous) effects as
well as on purely neutral mutations.
9 The nearly neutral theory can explain most observations
about molecular evolution, including the observations
that were problematic for the original purely
neutral theory. Critics argue that the nearly neutral
theory must invoke unrealistic assumptions about
population size in order to explain all the observations.
10 The neutral theory explains the higher evolutionary
rate of functionally less constrained regions of
proteins by the greater chance that a mutation there
will be neutral.
11 Pseudogenes and synonymous changes may be
relatively functionally unconstrained. They have faster
rates of evolution than non-synonymous changes, which
alter the amino acid sequence of the protein. This high
rate of evolution is probably due to enhanced neutral
drift.
12 Genomic data can be used to study natural
selection.
13 A high rate of non-synonymous evolution relative
to synonymous evolution suggests that natural selection
has been operating.
14 The McDonald–Kreitman test notes that the ratio
of non-synonymous to synonymous evolution (dN/dS
ratio) is equal between species and within a species
when drift operates, but differs between and within
species when selection operates.
15 The dN/dS ratio down the genome can be used to
identify sites where selection has acted. It can also be
used to estimate the fraction of sites where selection
has acted. Preliminary work suggests that about half
non-synonymous substitutions are by selection and
half by drift.
16 Biases in codon usage can be caused by natural
selection acting against certain codons in a synonymous
set, and by biased mutation. For single-celled
organisms, natural selection seems to explain the
patterns of codon usage bias.